Our rationale is to utilize existing mouse and rat epidermal systems for developing a suitable protocol(s) for human subjects. The approach to this problem will be to induce malignant transformation in animal in vitro systems, to identify nutritional, morphologic, ultrastructural, biochemical and enzymatic markers coincident with malignant transformation, to identify early markers which precede malignant transformation but need not be causal to it, and to correlate the appearance of early markers with malignant transformation in vivo and in vitro with strains of mice and rats which vary in susceptibility to known carcinogens. Early markers which correlate with malignant transformation in epidermal systems will also be tested for coincidence in other organs. The long-term objective of this research project is to identify early markers of malignant transformation for an epidemiological survey of human populations.